This project focuses on HIV-1 replication in cultured cells to develop understandings of viral pathogenesis and the cellular factors that influence viral gene expression. Important scientific advances that we have achieved in the 2009 to 2010 period include the following. 1) We have identified 252 cellular proteins that are important for HIV-1 replication in human T cells. 2) We have performed high throughput pyrosequencing of HIV-1 infected cells to identify changes in cellular small RNAs and a distribution of virus-produced small RNAs in cells. 3) We have characterized the role of an RNA-cap hypermethylating enzyme in regulating the expression of Rev-RRE-dependant HIV-1 unspliced/partially spliced RNAs.